High-throughput screen identifies metabolite regulators of endothelial function
Abstract
Endothelial cells (ECs) line blood vessels, regulate organ homeostasis, and their dysfunction is central to the development of cardiovascular diseases. Metabolites are critical regulators of EC health and function, yet only a limited number of metabolites that impact ECs have been identified. Here, we undertook a high-throughput screen of 884 metabolites and common drugs found in human biofluids to systematically identify compounds that impact barrier function in primary human umbilical vein ECs (HUVECs). Seven metabolites that deregulate vascular barrier function without causing cell death were shortlisted. These include (-)-epigallocatechin gallate, (±)-3-methyl-2-oxovaleric acid, taurocholic acid, myricetin, meloxicam, hesperetin and trans-3-indoleacrylic acid. These metabolites elicited differential effects on HUVECs, coronary artery ECs and pulmonary ECs. Transcriptional profiling revealed that each of the seven metabolites triggered distinct transcriptional responses in ECs, suggesting distinct mechanisms triggering EC barrier disruption. Notably, trans-3-indoleacrylic acid deregulated VE-cadherin junctions and increased EC sprouting, suggesting a potential role in angiogenesis. Together, these results provide a screening resource for metabolite-endothelial interactions and identify candidate circulating metabolites that regulate endothelial function.
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BibTeX
@article{oliveira2026highthroughput,
title = {{High-throughput screen identifies metabolite regulators of endothelial function}},
author = {Fabiana Oliveira and Olga Bondareva and Anne Hoffmann and Florian Geier and Anastasia Kyselova and Christina Karantanou and Sofia-Iris Bibli and Bilal N. Sheikh},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73615-3},
url = {https://www.nature.com/articles/s41598-026-73615-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High-throughput screen identifies metabolite regulators of endothelial function
AU - Fabiana Oliveira
AU - Olga Bondareva
AU - Anne Hoffmann
AU - Florian Geier
AU - Anastasia Kyselova
AU - Christina Karantanou
AU - Sofia-Iris Bibli
AU - Bilal N. Sheikh
PY - 2026
DA - 2026/10/01
JO - Scientific Reports
DO - 10.1038/s41598-026-73615-3
UR - https://www.nature.com/articles/s41598-026-73615-3
AB - Endothelial cells (ECs) line blood vessels, regulate organ homeostasis, and their dysfunction is central to the development of cardiovascular diseases. Metabolites are critical regulators of EC health and function, yet only a limited number of metabolites that impact ECs have been identified. Here, we undertook a high-throughput screen of 884 metabolites and common drugs found in human biofluids to systematically identify compounds that impact barrier function in primary human umbilical vein ECs (HUVECs). Seven metabolites that deregulate vascular barrier function without causing cell death were shortlisted. These include (-)-epigallocatechin gallate, (±)-3-methyl-2-oxovaleric acid, taurocholic acid, myricetin, meloxicam, hesperetin and trans-3-indoleacrylic acid. These metabolites elicited differential effects on HUVECs, coronary artery ECs and pulmonary ECs. Transcriptional profiling revealed that each of the seven metabolites triggered distinct transcriptional responses in ECs, suggesting distinct mechanisms triggering EC barrier disruption. Notably, trans-3-indoleacrylic acid deregulated VE-cadherin junctions and increased EC sprouting, suggesting a potential role in angiogenesis. Together, these results provide a screening resource for metabolite-endothelial interactions and identify candidate circulating metabolites that regulate endothelial function.
SN - 2045-2322
ER -